Introduction
Air enters the lung while breathing and fills alveoli, which are tiny air sacs. A capillary bed (a small network of blood vessels) surrounds these alveoli. Alveoli and capillaries must be properly aligned to exchange oxygen and carbon dioxide efficiently. Gas exchange can be hampered if capillaries are far from the alveoli surface or insufficient capillaries. Therefore, this results in insufficient oxygen supply throughout the body and makes the heart work harder. This article reviews one of the congenital disorders of alveoli in newborns.
What Is Alveolar Capillary Dysplasia?
MacMohan was the first to describe the disorder in 1947. A rare and lethal illness in neonates, alveolar capillary dysplasia, affects the blood vessels and gas exchange between the lungs. Millions of lung alveoli and capillaries within the alveoli are affected. The failure of capillaries to form in the right quantity and location inside the alveolar tissue of the lung, together with immature lobular development, leads to the condition's misalignment of lung vasculature, causing an inadequate and inefficient gas exchange. Early postnatal respiratory distress, chronic fetal circulation, and pulmonary hypertension that does not respond to supportive treatments can all be caused by alveolar capillary dysplasia.
In healthy humans, blood reaches capillaries through arteries. The veins carry deoxygenated blood from the capillaries to the heart. But in newborns with the disorder, the arteries and veins are bundled together, and the smooth muscle of arteries becomes thick, restricting blood flow. As a result, the heart has to work harder, and the blood pressure in the pulmonary arteries rises. All these conditions culminate in pulmonary hypertension, a pathognomic feature of the disease. Most people have additional conditions, including aberrant twisting of the big intestine or gastrointestinal system malformations from birth. Occasionally, newborns will also exhibit genitourinary and cardiovascular problems.
What Is the Incidence of Alveolar Cell Dysplasia?
There are only a few hundred reported cases of alveolar cell dysplasia. The spread of the ailment is widespread, and there is no geographic pattern for its onset. There are reports of slight male predominance. Almost 90 % of infants are born preterm, and more than 60 % develop respiratory failure or cyanosis (bluish discoloration) within 48 hours of birth.
What Causes Alveolar Cell Dysplasia?
The condition results from a mutation in the FOXF1 (forkhead box F1) gene. The gene encodes for a protein that binds with specific DNA (deoxyribonucleic acid) regions that help control the activities of other genes. The lungs, blood vessels, and digestive system all develop due to this gene. Any gene mutation generates an inactive protein that cannot control development and leads to improper construction of the gastrointestinal tract and pulmonary blood vessels.
In addition, deleting genetic information from chromosomes can cause the condition. Production of proteins is reduced when all of the FOXF1 genes are deleted from a chromosome. Deficient protein production affects pulmonary blood vessel development and predominant features of the disease. Further problems, like cardiac malformations, can result when the gene is missing. However, in 60 % of infants with the disorder, the cause remains unknown. Because affected newborns do not live long enough to reproduce, the condition cannot be passed down through the generations. The mortality rate in infants with this disorder is close to 100 %.
What Are the Signs and Symptoms of Alveolar Cell Dysplasia?
The disorder presents itself during the early period of infancy. During the first few days of life, affected newborns experience acute illness, severe hypoxemia, and pulmonary hypertension. However, there are some reports on clinical presentation after the neonatal period in patients with atypical or late manifesting alveolar cell dysplasia. Therefore, this suggests that infants with a milder disease can survive longer. Almost 80 % of infants with this disorder have associated anomalies of cardiovascular, urogenital, gastrointestinal, and musculoskeletal systems.
Initially, the clinical symptoms resemble idiopathic pulmonary hypertension in newborns. However, infants with alveolar dysplasia do not respond or transiently respond to treatment that can resolve idiopathic pulmonary hypertension. Alveolar cell dysplasia does not improve even with mechanical ventilation, nitric oxide, or ECMO (extracorporeal membrane oxygenation) treatment.
How Is Alveolar Cell Dysplasia Diagnosed?
Infants with severe hypoxemia and idiopathic pulmonary hypertension who are unresponsive after 7 to 10 days of neonatal intensive care treatment must undergo diagnostic testing. The initial chest radiograph reports may be normal. The infants present with less than 30 mm Hg (millimeters of mercury) of partial pressure oxygen in arterial blood, severe metabolic acidosis associated with pulmonary hypertensive crisis, and right ventricular failure. Other health anomalies also develop that pose difficulty in diagnosis. In infants with cardiac problems, cardiac catheterization can result in the absence of the capillary blush phase.
A confirmatory diagnosis for alveolar cell dysplasia is lung biopsy or autopsy. Lack of alveolar capillaries, expanded alveolar septae and enhanced pulmonary arteriole muscularization are pathological characteristics to look for in tissues. If alveolar cell dysplasia is suspected, several lung sections must be investigated because the disease may have a localized distribution.
What Is the Differential Diagnosis for Alveolar Capillary Dysplasia?
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Idiopathic neonatal pulmonary hypertension: The condition is distinguished from alveolar cell dysplasia because it can be treated and reversed. When pulmonary vasodilators, respiratory assistance, or ECMO are used as treatment, the condition disappears.
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Sepsis, pneumonia, and other lung infections.
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Congenital diaphragmatic hernia, pulmonary hypoplasia, anomalies in surfactant production, and rare diffuse interstitial illnesses are examples of primary respiratory problems.
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Congenital cardiopulmonary diseases are associated with severe cyanosis and pulmonary hypertension.
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Congenital neuromuscular disease and neonatal hypoxia are two examples of neurological conditions.
How Is Alveolar Cell Dysplasia Treated?
Treatment for alveolar cell dysplasia is through the following ways:
Standard Therapy
It includes mechanical ventilation, high concentration of inspired oxygen, inhalational nitric oxide, and ECMO support. These treatments can add days or weeks to the infant's life but are ineffective for long-term survival.
Investigational Therapy
Lung transplantation is the only treatment option because conventional medication is ineffective in ensuring infants' long-term survival. Diagnosing the disease early with lung biopsy and planning strategies for the infant's long-term survival can help manage the condition efficiently. However, lung donor availability may hinder the treatment procedure.
Conclusion
Alveolar cell dysplasia is a life-threatening disorder in newborns that disrupts gas exchange and results in severe hypoxemia and pulmonary hypertension. Histological examination of lung tissue or autopsy are the only possible investigative procedures. Although the infants are treated, their long-term survivability remains poor.
